In Aplysia, the activation of MAPK is required for certain forms of long-lasting synaptic facilitation and memory for sensitization. Moreover, multiple serotonin (5-HT) pulses, as well as, memory inducing stimuli (repeated tail shocks) produce sustained MAPK activation. However, several key questions remain unanswered. For instance: (1) What are the temporal dynamics of 5-HT induced MAPK activation? (2) What additional pathways are responsible for MAPK activation? (3) Do activity-dependent intermediate-term synaptic facilitation (ITF) and memory for sensitization (ITM) require MAPK activity? and (4) Do long-term synaptic facilitation (LTF) and memory for sensitization (LTM) require persistent MAPK activation? These questions form the core of this proposal. Specific phases of investigation will consist of molecular, synaptic and behavioral levels of analyses. The molecular phase of the project will examine the mechanisms of calcium dependent MAPK activation, and 5-HT induced persistent MAPK activity. The functional consequences of these dual activation pathways will be investigated at the synaptic and behavioral levels of analyses. Two hypotheses will be tested: (1) That calcium dependent MAPK activation is specifically required for activity-dependent ITF and ITM, and (2) that persistent MAPK activation is selectively recruited for the induction of LTF and LTM.